Concurrent Sessions - Transitioning from Academic Probation to Academic Progress: A Success Focused Review

In this Project/Research Reporting session we will briefly describe our former system of Academic Probation and discuss the messages this system sent to students and the fiscal and staffing burdens it placed on the college. We will then discuss the benefits of our redesigned process, describe the new interventions, and logistical considerations for implementation as well as the relevant assessment data to date. This session will wrap up with a discussion/question and answer period. This session is applicable to all sectors of higher education and relevant to all professionals

Modeling a century of citation distributions

The prevalence of uncited papers or of highly cited papers, with respect to the bulk of publications, provides important clues as to the dynamics of scientific research. Using 25 million papers and 600 million references from the Web of Science over the 1900–2006 period, this paper proposes a simple model based on a random selection process to explain the “uncitedness” phenomenon and its decline over the years. We show that the proportion of cited papers is a function of (1) the number of articles available (the competing papers), (2) the number of citing papers and (3) the number of references they contain. Using uncitedness as a departure point, we demonstrate the utility of the stretched-exponential function and a form of the Tsallis q-exponential function to fit complete citation distributions over the 20th century. As opposed to simple power-law fits, for instance, both these approaches are shown to be empirically well-grounded and robust enough to better understand citation dynamics at the aggregate level. On the basis of these models, we provide quantitative evidence and provisional explanations for an important shift in citation practices around 1960. We also propose a revision of the “citation classic” category as a set of articles which is clearly distinguishable from the rest of the field

Identification and Validation of Small Molecules That Enhance Recombinant Adeno-associated Virus Transduction following High-Throughput Screens

ABSTRACT While the recent success of adeno-associated virus (AAV)-mediated gene therapy in clinical trials is promising, challenges still face the widespread applicability of recombinant AAV(rAAV). A major goal is to enhance the transduction efficiency of vectors in order to achieve therapeutic levels of gene expression at a vector dose that is below the immunological response threshold. In an attempt to identify novel compounds that enhance rAAV transduction, we performed two high-throughput screens comprising 2,396 compounds. We identified 13 compounds that were capable of enhancing transduction, of which 12 demonstrated vector-specific effects and 1 could also enhance vector-independent transgene expression. Many of these compounds had similar properties and could be categorized into five groups: epipodophyllotoxins (group 1), inducers of DNA damage (group 2), effectors of epigenetic modification (group 3), anthracyclines (group 4), and proteasome inhibitors (group 5). We optimized dosing for the identified compounds in several immortalized human cell lines as well as normal diploid cells. We found that the group 1 epipodophyllotoxins (teniposide and etoposide) consistently produced the greatest transduction enhancement. We also explored transduction enhancement among single-stranded, self-complementary, and fragment vectors and found that the compounds could impact fragmented rAAV2 transduction to an even greater extent than single-stranded vectors. In vivo analysis of rAAV2 and all of the clinically relevant compounds revealed that, consistent with our in vitro results, teniposide exhibited the greatest level of transduction enhancement. Finally, we explored the capability of teniposide to enhance transduction of fragment vectors in vivo using an AAV8 capsid that is known to exhibit robust liver tropism. Consistent with our in vitro results, teniposide coadministration greatly enhanced fragmented rAAV8 transduction at 48 h and 8 days. This study provides a foundation based on the rAAV small-molecule screen methodology, which is ideally used for more-diverse libraries of compounds that can be tested for potentiating rAAV transduction. IMPORTANCE This study seeks to enhance the capability of adeno-associated viral vectors for therapeutic gene delivery applicable to the treatment of diverse diseases. To do this, a comprehensive panel of FDA-approved drugs were tested in human cells and in animal models to determine if they increased adeno-associated virus gene delivery. The results demonstrate that particular groups of drugs enhance adeno-associated virus gene delivery by unknown mechanisms. In particular, the enhancement of gene delivery was approximately 50 to 100 times better with than without teniposide, a compound that is also used as chemotherapy for cancer. Collectively, these results highlight the potential for FDA-approved drug enhancement of adeno-associated virus gene therapy, which could result in safe and effective treatments for diverse acquired or genetic diseases

An Initial Report of Sleep Disorders in Women in the U.S. Military

The article of record as published may be found at http://dx.doi.org/10.1093/milmed/usx116Sleep disorders are increasingly recognized in active duty service members (ADSM). While there are multiple studies in male ADSM, there are limited data regarding sleep disorders in women in the military. The purpose of this study was to characterize sleep disorders in female ADSM referred for clinical evaluation to provide a better understanding of this unique population. Materials and Methods: We conducted a retrospective review of female ADSM who underwent a sleep medicine evaluation and an attended polysomnogram (PSG). Demographic and polysomnogram variables, as well as medical records, were reviewed. Associated illnesses to include post-traumatic stress disorder, pain disorders, anxiety, and depression, were recorded. Results: The cohort consisted of 101 women. The average age was 33.9 ± 9.0 years and body mass index was 27.3 ± 4.5, with an average Epworth Sleepiness Scale score of 12.9 ± 5.2, and Insomnia Severity Index score of 17.6 ± 5.7. Overall, 36.6% were diagnosed with insomnia only, 14.9% with obstructive sleep apnea (OSA) only, and 34.7% met diagnostic criteria for both insomnia and OSA. The average apnea-hypopnea index for the entire cohort was 5.37 ± 7.04/h whereas it was 10.34 ± 3.14/h for those meeting diagnostic criteria for OSA. The women referred for sleep evaluations had the following rates of associated illnesses: pain disorders (59.4%), anxiety (48.5%), depression (46.5%), and post-traumatic stress disorder (21.8%). For patients with OSA, the relative risk of having post-traumatic stress disorder was 2.72 (95% confidence interval 1.16–6.39). Conclusions: Women in the U.S. military who have sleep disorders have a high rate of behavioral medicine and pain disorders. Interestingly, nearly 50% of active duty females referred for a sleep study have OSA while not necessarily manifesting the typical signs of obesity or increased age. The reasons for this finding are not completely understood, though factors related to military service may potentially contribute. The findings from our study indicate a need for increased awareness and evaluation of sleep disorders in women in the military, especially those with behavioral medicine disorders

Spontaneous virologic suppression in HIV controllers is independent of delayed-type hypersensitivity test responsiveness

<p>Abstract</p> <p>Background</p> <p>Delayed-type hypersensitivity (DTH) testing, an in vivo assessment of cell-mediated immunity, is a predictor of HIV disease progression beyond CD4 cell count. We investigated whether preserved DTH responsiveness was characteristic of HIV controllers compared to non-controllers and individuals on suppressive HAART.</p> <p>Findings</p> <p>DTH testing consisted of ≥ 3 recall antigens applied approximately every 6 months. DTH responses were classified by the number of positive skin tests: anergic (0), partial anergic (1), or non-anergic (≥ 2). HIV controllers were compared to treatment naïve non-controllers (n = 3822) and a subgroup of non-controllers with VL < 400 copies/mL on their initial HAART regimen (n = 491). The proportion of non-anergic results at first DTH testing was similar for HIV controllers compared to non-controllers (81.9% vs. 77.6%; P = 0.22), but tended to be greater in HIV controllers compared to the HAART subgroup (81.9% vs. 74.5%; P = 0.07). Complete anergy was observed in 14 (10.1%) HIV controllers with CD4 counts ≥ 400 cells/uL. For longitudinal testing, the average percentage of non-anergic DTH determinations per participant was higher in HIV controllers compared to non-controllers (81.2 ± 31.9% vs. 70.7 ± 36.8%; P = 0.0002), however this difference was eliminated with stratification by CD4 count: 200-399 (83.4 ± 35.6% vs. 71.9 ± 40.9%; P = 0.15) and > 400 cells/uL (81.2 ± 31.5% vs. 80.4 ± 32.7%; P = 0.76).</p> <p>Conclusions</p> <p>Spontaneous virologic control was not associated with DTH responsiveness, and several HIV controllers were anergic despite having elevated CD4 counts. These findings suggest that cellular immunity assessed by DTH is not a principal factor contributing to spontaneous virologic suppression in HIV controllers.</p

Assessing the contributions of childhood maltreatment subtypes and depression case-control status on telomere length reveals a specific role of physical neglect

Background: Studies have provided evidence that both childhood maltreatment and depressive disorders are associated with shortened telomere lengths. However, as childhood maltreatment is a risk factor for depression, it remains unclear whether this may be driving shortened telomere lengths observed amongst depressed patients. Furthermore, it's unclear if the effects of maltreatment on telomere length shortening are more pervasive amongst depressed patients relative to controls, and consequently whether biological ageing may contribute to depression's pathophysiology. The current study assesses the effects of childhood maltreatment, depression case/control status, and the interactive effect of both childhood maltreatment and depression case/control status on relative telomere length (RTL). Method: DNA samples from 80 depressed subjects and 100 control subjects were utilized from a U.K. sample (ages 20-84), with childhood trauma questionnaire data available for all participants. RTL was quantified using quantitative polymerase chain reactions. Univariate linear regression analyses were used to assess the effects of depression status, childhood maltreatment and depression by childhood maltreatment interactions on RTL. The false discovery rate (q 50 years old). There were no significant depression case/control status by childhood maltreatment interactions. Limitations: A relatively small sample limited our power to detect interaction effects, and we were unable to consider depression chronicity or recurrence. Conclusion: Shortened RTL was specifically associated with childhood physical neglect, but not the other subtypes of maltreatment or depression case/control status. Our results suggest that the telomere-eroding effects of physical neglect may represent a biological mechanism important in increasing risk for ageing-related disorders. As physical neglect is more frequent amongst depressed cases generally, it may also represent a confounding factor driving previous associations between shorter RTL and depression case status.Peer reviewe

Delivering a “Dose of Hope”: A Faith-Based Program to Increase Older African Americans’ Participation in Clinical Trials

Background: Underrepresentation of older-age racial and ethnic minorities in clinical research is a significant barrier to health in the United States, as it impedes medical research advancement of effective preventive and therapeutic strategies. Objective: The objective of the study was to develop and test the feasibility of a community-developed faith-based intervention and evaluate its potential to increase the number of older African Americans in clinical research. Methods: Using a cluster-randomized design, we worked with six matched churches to enroll at least 210 persons. We provided those in the intervention group churches with three educational sessions on the role of clinical trials in addressing health disparity topics, and those in the comparison group completed surveys at the same timepoints. All persons enrolled in the study received ongoing information via newsletters and direct outreach on an array of clinical studies seeking participants. We evaluated the short-, mid-, and longer-term effects of the interventional program on clinical trial-related outcomes (ie, screening and enrollment)

A comparison of calcium to zoledronic acid for improvement of cortical bone in an animal model of CKD

Bone Biology Laboratory http://www.iupui.edu/~bonelab/ Department of Anatomy and Cell Biology Indiana University School of MedicinePatients with chronic kidney disease (CKD) have increased risk of fractures, yet the optimal treatment is unknown. In secondary analyses of large randomized trials, bisphosphonates have been shown to improve bone mineral density and reduce fractures. However, bisphosphonates are currently not recommended in patients with advanced kidney disease due to concern about over-suppressing bone remodeling, which may increase the risk of developing arterial calcification. In the present study we used a naturally occurring rat model of CKD with secondary hyperparathyroidism, the Cy/+ rat, and compared the efficacy of treatment with zoledronic acid, calcium given in water to simulate a phosphate binder, and the combination of calcium and zoledronic acid. Animals were treated beginning at 25 weeks of age (approximately 30% of normal renal function) and followed for ten weeks. The results demonstrate that both zoledronic acid and calcium improved bone volume by microCT and both equally suppressed mineral apposition rate, bone formation rate, and mineralizing surface of trabecular bone. In contrast, only calcium treatment with or without zoledronic acid improved cortical porosity and cortical biomechanical properties (ultimate load and stiffness) and lowered parathyroid hormone (PTH). However, only calcium treatment led to the adverse effects of increased arterial calcification and fibroblast growth factor 23 (FGF23). These results suggest zoledronic acid may improve trabecular bone volume in CKD in the presence of secondary hyperparathyroidism, but does not benefit extraskeletal calcification or cortical biomechanical properties. Calcium effectively reduces PTH and benefits both cortical and trabecular bone yet increases the degree of extra skeletal calcification.This work was supported by the NIH NIAMS R01 5R01AR058005 (SMM) and S10-RR023710 (microCT equipment grant). We thank Drew Brown for tissue dissections, CT scanning and analysis